Peptide-in-groove interactions link target proteins to the beta-propeller of clathrin

The "WD40" domain is a widespread recognition module for linking partner pr oteins in intracellular networks of signaling and sorting. The clathrin ami no-terminal domain, which directs incorporation of cargo into coated pits, is a beta-propeller closely related in structure to WD40 modules. The cryst allographically determined structures of complexes of the clathrin-terminal domain with peptides derived from two different cargo adaptors, beta-arres tin 2 and the beta-subunit of the AP-3 complex, reveal strikingly similar p eptide-in-groove interactions. The two peptides in our structures contain r elated, five-residue motifs, which form the core of their contact with clat hrin. A number of other proteins involved in endocytosis have similar "clat hrin-box" motifs, and it therefore is likely that they all bind the termina l domain in the same way. We propose that a peptide-in-groove interaction i s an important general mode by which beta-propellers recognize specific tar get proteins.